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Verdinexor (KPT-335)

现货
Catalog No.
B4889
XPO1/CRM1抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,500.00
现货
5mg
¥ 1,400.00
现货
25mg
¥ 4,700.00
现货

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Background

Verdinexor (KPT-335) is a potent and selective inhibitor of nuclear export [1].

Nuclear export (SINE) is mainly mediated by exportin 1 (XPO1) and mediates specific proteins out of the nucleus, which plays an important role in the regulation of proliferation and the cell cycle [2].

Verdinexor (KPT-335) is a potent and selective SINE inhibitor that acts as an antiviral drug. In A549 cells inoculated with the influenza A and B virus, verdinexor effectively inhibited the replication of the influenza A and B virus strains tested. verdinexor (1 µM) caused the accumulation of vRNPs in the nuclei and altered the localization of viral NS1. Also, verdinexor increased nuclear negative-sense vRNA by 56.6-fold and significantly reduced cytoplasmic negative-sense vRNA, which suggested that verdinexor blocked vRNP nuclear export. In 293T cells, verdinexor inhibited XPO1-NEP binding [1].

In mice infected with influenza virus A, verdinexor significantly reduced lung influenza virus A titers. Verdinexor also reduced the expression of proinflammatory cytokines tumor necrosis factor alpha, interleukin-6, interleukin-1β and gamma interferon. In mice infected with a lethal dose, verdinexor inhibited virus penetration of the respiratory tract and virus spread in the lungs [1]. In companion dogs with B- and T-cell lymphomas, verdinexor showed potent cytotoxic activity [2].

References:
[1].  Perwitasari O, Johnson S, Yan X, et al. Verdinexor, a novel selective inhibitor of nuclear export, reduces influenza a virus replication in vitro and in vivo. J Virol, 2014, 88(17): 10228-10243.
[2].  Gravina GL, Senapedis W, McCauley D, et al. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol, 2014, 7: 85.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt442.32
Cas No.1392136-43-4
FormulaC18H12F6N6O
Solubility≥44.2mg/mL in DMSO
Chemical Name(Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-N'-pyridin-2-ylprop-2-enehydrazide
SDFDownload SDF
Canonical SMILESC1=CC=NC(=C1)NNC(=O)C=CN2C=NC(=N2)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验:

细胞系

人A549细胞

溶解方法

在DMSO中的溶解度大于10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

2 h,1 μM

应用

Verdinexor (KPT-335)是一种可口服的选择性出核转运抑制剂。它可以阻止子代流感病毒基因组的出核,抑制H1N1,H5N1和H7N9等多种流感病毒的复制。Verdinexor (KPT-335)可以破坏XPO1蛋白与NEP蛋白的结合,从而阻断多种甲型流感病毒vRNP复合物的出核[1]。此外,在犬类黑素瘤细胞中,Verdinexor (KPT-335)还具有抑制增殖和诱导凋亡的效果[2]。

动物实验 [3]:

动物模型

雌性BALB/c小鼠6-8周龄

剂量

20 mg/kg,口服给药,2天1次

应用

在小鼠中,Verdinexor (KPT-335)能够有效抑制病毒脱落,减缓白细胞渗透到支气管肺泡空间,降低肺中促炎细胞因子的表达。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Perwitasari O, Johnson S, Yan X, et al. Verdinexor, a novel selective inhibitor of nuclear export, reduces influenza a virus replication in vitro and in vivo[J]. Journal of virology, 2014, 88(17): 10228-10243.

[2]. Breit M N, Kisseberth W C, Bear M D, et al. Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines[J]. BMC veterinary research, 2014, 10(1): 1.

[3]. Perwitasari O, Johnson S, Yan X, et al. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection[J]. PloS one, 2016, 11(11): e0167221.

质量控制

化学结构

Verdinexor (KPT-335)